Safety and Efficiency of VRd Combining BCMA CAR-T Regimen for Transplant-ineligible Patients With Primary Plasma Cell Leukemia: a Prospective, Single-arm, Single-center, Phase II Study.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Safety and Tolerability
研究概览
简要总结
This is a single-arm, open-label study to evaluate the efficacy and safety of VRD-based regimen combined with BCMA CAR-T in transplant-ineligible patients with primary plasma cell leukemia
详细描述
The study is a prospective, single-arm, single-centre, phase II study designed to evaluate the efficacy and safety of treatment with VRD-based regimen combined with BCMA CAR-T in transplant-ineligible patients with primary plasma cell leukemia. Patients received 3 courses of induction therapy with VRD-based regimen followed by infusion of BCMA CAR-T cells. Patients then received 3 courses of VR consolidation therapy, followed by VR maintenance therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years and ≤ 75 years.
- •Participants with documented primary plasma cell leukemia according to IMWG diagnostic criteria (circulating plasma cells ≥5%, determined by morphology on peripheral blood smear; or absolute value of peripheral blood tumorigenic plasma cells exceeds 2×10^9/L).
- •Measurable disease, at screening as defined by any of the following: Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or Light chain MM without measurable disease in serum or urine: serum Ig free-light chain (FLC) ≥10 mg/dL and abnormal serum Ig kappa lambda FLC ratio.
- •Not considered for high-dose chemotherapy with Autologous Stem Cell Transplant (ASCT) due to: Ineligible due to advanced age (≥65); or Ineligible evaluated by researchers; or Eastern Cooperative Oncology Group Performance Status grade of 3 or 4; or Repeated hematopoietic stem cell mobilization failure； or Deferral of high-dose chemotherapy with ASCT as initial treatment.
- •Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological examination.
- •All screening blood biochemistry: tests should be performed according to the protocol and within 14 days before enrollment. Screening laboratory values must meet the following criteria: a.TBIL<2 x upper limit of normal (ULN) (<3 x ULN in patients with Gilbert's syndrome); b.AST and ALT <3 x ULN.; c. Creatinine clearance ≥ 30mL/min (calculated using Cockroft-Gault formula).
- •Routine blood tests (performed within 7 days, no RBC transfusion, no G-CSF/GM-CSF/platelet agonists, no drug correction within 14 days before screening, no PLT transfusion within 7 days) : WBC ≥ 1.5 x 109/L, ANC ≥ 1.0 x 109/L, Hb ≥ 70 g/L PLT ≥ 75 x 109/L (if BMPC < 50%) or PLT ≥ 50 x 109/L (if BMPC ≥ 50%).
- •Patients must be able to take prophylactic anticoagulant therapy as recommended by the study.
- •The woman is not breastfeeding, is not pregnant and agrees not to be pregnant during the study period and for the following 12 months. Male patients agreed that their spouse would not become pregnant during the study period and for 12 months thereafter.
排除标准
- •Documented active amyloidosis.
- •Documented with central nervous system (CNS) invasion.
- •Prior exposure to any BCMA-targeted therapy or CAR-T therapy.
- •Patients with peripheral neuropathy greater than grade 2 or peripheral neuropathy greater than grade 2 with pain at baseline, regardless of whether they were currently receiving medical therapy.
- •Known intolerance, hypersensitivity, or contraindication to glucocorticoids, bortezomib, lenalidomide, and BCMA-CART cellular products.
- •Seropositive for human immunodeficiency virus (HIV)
- •Hepatitis B infection
- •Hepatitis C infection
- •Life expectancy of <6 months
- •Women who are pregnant or breastfeeding
- •Any active gastrointestinal dysfunction that affects the patient's ability to swallow tablets, or any active gastrointestinal dysfunction that may affect the absorption of the studied treatment medication
- •Subjects had major surgery within 2 weeks before randomization (for example, general anesthesia), or is not fully recovered from the surgery, or surgery is arranged during study period.
- •Received live attenuated vaccine within 4 weeks prior to study treatment.
- •According to the researcher's judgment, any condition including but not limited to serious mental illness, medical illness, or other symptoms/conditions that may affect study treatment, compliance, or the capability of providing informed consent.
- •Necessary medication or supportive therapy is contraindicated with study treatment.
- •Any diseases or complications that may interfere with the study.
- •Patients are not willing to or cannot comply with study scheme.
研究组 & 干预措施
VRD-based Regimen Combined With BCMA CART
VRD：Bortezomib, Lenalidomide and Dexamethasone Bortezomib SC 1.3mg/sqm on day 1,8,15,22, Lenalidomide oral 25 mg on day 1-21, and Dexamethasone 40mg on day 1,8,15,22 in a 28-day cycle.
Autologous BCMA-directed CAR-T cells, infusion intravenously at a target dose of 2-4 x 10^6 anti-BCMA CAR+T cells/kg.
Participants will receive VRD-based induction, BCMA CAR-T infusion, VR consolidation, VR maintenance.
干预措施: anti-BCMA CAR-T (Biological)
VRD-based Regimen Combined With BCMA CART
VRD：Bortezomib, Lenalidomide and Dexamethasone Bortezomib SC 1.3mg/sqm on day 1,8,15,22, Lenalidomide oral 25 mg on day 1-21, and Dexamethasone 40mg on day 1,8,15,22 in a 28-day cycle.
Autologous BCMA-directed CAR-T cells, infusion intravenously at a target dose of 2-4 x 10^6 anti-BCMA CAR+T cells/kg.
Participants will receive VRD-based induction, BCMA CAR-T infusion, VR consolidation, VR maintenance.
干预措施: VRD-based regimen (Drug)
结局指标
主要结局
Safety and Tolerability
时间窗: Up to 2 year
The incidence of treatment-emergent adverse events (TEAEs)
MRD-negative rate
时间窗: within 1 week after consolidation treatment
achieving MRD-negative, as determined by NGS/NGF after consolidation treatment
次要结局
- Progression free survival (PFS)(Up to 2 year)
- Overall Survival (OS)(Up to 5 year)
- Duration of Remission(DOR)(Up to 2 year)
- Complete response rate (CRR)(within 1 week after induction therapy, 1 month after the CAR-T cell transfusion, within 1 week after consolidation therapy)